The US Food and Drug Administration's (FDA) Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) and Oncologic Drugs Advisory Committee (ODAC) are giving the green light to a new cancer immunotherapy by Amgen Inc. known as T-Vec (talimogene laherparepvec/BLA 125518).
The US Food and Drug Administration's (FDA) Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) and Oncologic Drugs Advisory Committee (ODAC) are giving the green light to a new cancer immunotherapy by Amgen Inc. known as T-Vec (talimogene laherparepvec/BLA 125518). This experimental treatment is for patients with injectable regionally or distantly metastatic melanoma. The joint committee panel raised concerns about the product’s effectiveness at a meeting, but supported traditional--not accelerated--approval of the drug.
Amgen researchers presented at the meeting the results of the pivotal phase III OPTiM study, which showed that T-Vec monotherapy is the first oncolytic immunotherapy to demonstrate therapeutic benefit in a phase III pivotal trial for patients with metastatic melanoma. T-Vec is an investigational oncolytic immunotherapy designed to selectively replicate in tumors and to initiate an immune response to target cancer cells that have metastasized.
T-Vec packs a two-pronged approach. It is injected directly into tumors where it replicates inside the tumor cells, causing the cell to rupture and die. Then, the rupture of the cancer cells release tumor-derived antigens, along with granulocyte macrophage colony-stimulating factor (GM-CSF) to stimulate a system-wide immune response.
Executive Vice President of Research and Development at Amgen Inc., Sean Harper, MD, said the incidence of melanoma has continued to rise over the last 30 years, even as many other cancers are in decline. He said despite recent advances there is still an unmet need in this disease.
Amgen Inc. has in place a comprehensive clinical development program for T-Vec in metastatic melanoma. It includes combination studies with checkpoint inhibitors in patients with late-stage disease and neoadjuvant monotherapy in patients with resectable disease. T-Vec has the potential to be used in the treatment of a variety of solid tumor types based on its clinical profile.
Study 005/05, referred to as OPTiM, was a phase III, multicenter, open-label, randomized clinical trial comparing T-Vec to GM-CSF in patients with advanced melanoma (stage IIIB, IIIC, or IV) that was not surgically resectable. The primary endpoint of the study was durable response rate (DRR). In the 436-patient study, T-Vec significantly improved DRR with 16.3% of T-Vec treated patients achieving a complete response (CR) or partial response (PR) within the first 12 months of treatment, and maintaining it continuously for at least 6 months compared to 2.1% of patients treated with GM-CSF.
In patients with stage III/IV metastatic melanoma, there was an improved overall (CR and PR) response rate compared with GM-CSF (26.4% vs 5.7%, respectively), and the median OS was 4.4 months longer in the T-Vec arm than in the GM-CSF arm.
The most commonly reported treatment-related adverse events (AE) were fatigue, chills, pyrexia, nausea, influenza-like illness, and injection site pain. Most adverse reactions reported were mild or moderate in severity and generally resolved within 72 hours. The most common serious adverse reaction was cellulitis.
A final decision by the FDA is expected by October 2015.